Gas collection and analysis system with front-end and back-end pre-concentrators and moisture removal

ABSTRACT

Embodiments of an apparatus including a front-end pre-concentrator module including an inlet, an outlet, and at least one valve to control flow through the inlet, the outlet, or both. The apparatus includes a back-end pre-concentrator module including an inlet, an outlet, and at least one valve to control flow through the inlet, the outlet, or both, and also includes a gas analysis module having an inlet and an outlet and including a gas chromatograph having an inlet and an outlet. The outlet of the front-end pre-concentrator and the outlet of the back-end pre-concentrator are coupled to the inlet of the gas analysis module. Other embodiments are also disclosed and claimed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of its parent application, U.S.application Ser. No. 12/847,593, filed 30 Jul. 2010 and still pending,and claims priority thereto under 35 U.S.C. §120. The parent applicationin turn claims priority under 35 U.S.C. §119(e) to U.S. ProvisionalPatent Application No. 61/230,647, filed 31 Jul. 2009, and U.S.Provisional Patent Application No. 61/326,433, filed 21 Apr. 2010. Bothprovisional applications are incorporated herein by reference in theirentirety.

TECHNICAL FIELD

The present invention relates generally to gas analysis systems and inparticular, but not exclusively, to handheld gas analysis systemsincluding front-end pre-concentrators, back-end pre-concentrators andmoisture removal.

BACKGROUND

Gas analysis can be an important means for detecting the presence andconcentration of certain chemicals in the gas and determining themeaning of the particular combination of chemicals present. In healthcare, for example, the presence of certain volatile organic compounds(VOCs) in exhaled human breath are correlated to certain diseases, suchas pneumonia, pulmonary tuberculosis (TB), asthma, lung cancer, liverdiseases, kidney diseases, etc. The correlations are especiallyevidential for lung-related diseases. In other applications, gasanalysis can be used to determine the presence of dangerous substancesincompatible with human presence, such as methane, carbon monoxide orcarbon dioxide in a mine.

Current gas analytical systems still rely heavily on large and expensivelaboratory instruments, such as gas chromatography (GC) and massspectrometry (MS). Most of these instruments (mass spectrometers inparticular) have operational characteristics that prevent significantreductions in their size, meaning that current gas analysis systems arelarge and expensive bench devices. In addition to being expensive andunwieldy, the large size of current gas analysis devices makeswidespread use of these instruments impossible.

Since the conventional GC/MS are bulky in size and expensive, theequipment is usually located in the labs and breath samples must becollected in the laboratories or by other on-site means. Two approacheshave been used for on-site breath collection. The canister breathcollection is the most commonly used approach: breath is inhaled andcollected into a pre-cleaned and pre-vacuumed bottle, and the bottle isthen sent to a lab for analysis. Such canisters are very expensive andalso require a very expensive cleaning system in order to re-use thecanister. As a result, the breath test cost cannot be reduced due tovery high cost in equipment and system setup. In another approach,instead of using a canister, a trap is used as an alternative on-sitebreath collection: the trap is located in a breath collection system,which monitors the amount of breath and condition during collection. Thetrap is then removed and then sent to lab for analysis using similar gasanalysis equipment for the canister approach. The trap approacheliminates the requirement of expensive cleaning tools, but the trapcollection system itself can be more expensive than the canister. Bothbreath collection and analysis approaches requires the breath collectionon-site and then the samples are sent back to labs for analysis, whichis time-consuming and very expensive.

Exhaled breath contains >90% humidity. When the moisture is collectedtogether with gases/volatile organic compounds (VOCs) from breath andthen directly injected into a gas analysis system, any significantamount of moisture will drastically reduce the analyzer sensitivity tochemicals/VOCs of interest. As a result, the system's detection limitbecomes much worse than the case when there is no or low moisturepresent. The current approach in moisture removal for breath analysis isto extract the collected breath sample from the container, which is usedto store breath from the subject. The sample is then extracted andinjected into a front-end moisture removal equipment. The equipmentcools down (condenses) the collected breath (including moisture) in atrap or tube to sub-zero Celsius temperature (by liquid nitrogen or dryice) and then heats up the trap to separate moisture from other gasesdue to different boiling temperatures. There can be multiple stages ofcryo-cooling and heating steps to remove moisture before gases/VOCs aretransferred into a gas chromatograph/mass spectrometer (GC/MS) systemfor analysis. Such front-end equipment is massive in size and highlyexpensive (>$20,000).

The existing approach requires expensive equipment setup and is bulky insize as described above. The breath analysis is performed in multiplestages. Breath first is collected in canister, trap, or other container.The sample is then transferred to laboratory, where the moisture removalsystem (front-end system) and gas/VOC analysis system (e.g., GC/MS) arelocated. The gases/VOCs and moisture are then extracted from the sampleto the front-end system for moisture removal before the gases/VOCs arefed into the analyzer (GC/MS). The equipment is expensive and notportable. Meanwhile, this breath collection and moisture removalprocedure cannot be used for in-situ breath analysis.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments of the present invention aredescribed with reference to the following figures, wherein likereference numerals refer to like parts throughout the various viewsunless otherwise specified.

FIG. 1A is a side elevation drawing of an embodiment of a gas analysisdevice.

FIG. 1B is a plan view of the embodiment of a gas analysis device shownin FIG. 1.

FIG. 2A is a cross-sectional elevation drawing of an embodiment of aMEMS pre-concentrator that can be used in the embodiment of a gasanalysis device shown in FIGS. 1A-1B.

FIG. 2B is a cross-sectional elevation drawing of an alternativeembodiment of a MEMS pre-concentrator that can be used in the embodimentof a gas analysis device shown in FIGS. 1A-1B.

FIG. 3A is a plan view drawing of an embodiment of a MEMS gaschromatograph that can be used in the embodiment of a gas analysisdevice shown in FIGS. 1A-1B

FIG. 3B is a cross-sectional elevation drawing of the embodiment of aMEMS gas chromatograph shown in FIG. 3A, taken substantially alongsection line B-B.

FIG. 4A is a plan view drawing of an embodiment of a detector array thatcan be used in the embodiment of a gas analysis device of FIGS. 1A-1B.

FIG. 4B is a cross-sectional elevation drawing of the embodiment of adetector array shown in FIG. 4A, taken substantially along section lineB-B.

FIG. 5 is a schematic diagram of an alternative embodiment of a gasanalysis device and an embodiment of a system using the embodiment ofthe gas analysis device.

FIG. 6 is a schematic diagram of another alternative embodiment of a gasanalysis device and an embodiment of a system using the embodiment ofthe gas analysis device.

FIG. 7 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

FIG. 8 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

FIG. 9 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

FIG. 10 is a schematic diagram of an embodiment of a gas analysis deviceincluding a front-end pre-concentrator module.

FIG. 11 is a drawing of an embodiment of a filter assembly that can beused with a gas analysis device.

FIG. 12A is a drawing of an embodiment of a pre-concentrator that can beused with an embodiment of a gas analysis system.

FIG. 12B is a drawing of an alternative embodiment of a pre-concentratorthat can be used with an embodiment of a gas analysis system.

FIG. 13A is a schematic diagram of an embodiment of a gas analysisdevice including front-end and back-end pre-concentrator modules.

FIG. 13B is a schematic diagram of an alternative embodiment of a gasanalysis device including front-end and back-end pre-concentratormodules.

FIG. 13C is a schematic diagram of another alternative embodiment of agas analysis device including front-end and back-end pre-concentratormodules.

FIG. 14 is a schematic diagram of yet another alternative embodiment ofa gas analysis device including front-end and back-end pre-concentratormodules.

FIG. 15 is a schematic diagram of an embodiment of a disposable filterassembly.

FIG. 16 is a schematic diagram of a pair of alternative embodiments of afilter assembly.

FIG. 17A-17B are schematic diagrams of additional alternativeembodiments of a disposable filter assembly.

FIG. 18 is a schematic diagram of an embodiment of a re-usablemoisture-removal assembly.

FIG. 19 is a schematic diagram of an alternative embodiment of are-usable moisture-removal assembly.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

Embodiments of an apparatus, process and system for gas analysis inpoint-of-care medical applications are described herein. In thefollowing description, numerous specific details are described toprovide a thorough understanding of embodiments of the invention. Oneskilled in the relevant art will recognize, however, that the inventioncan be practiced without one or more of the specific details, or withother methods, components, materials, etc. In other instances, wellknownstructures, materials, or operations are not shown or described indetail but are nonetheless encompassed within the scope of theinvention.

Reference throughout this specification to “one embodiment” or “anembodiment” means that a particular feature, structure, orcharacteristic described in connection with the embodiment is includedin at least one embodiment of the present invention. Thus, appearancesof the phrases “in one embodiment” or “in an embodiment” in thisspecification do not necessarily all refer to the same embodiment.Furthermore, the particular features, structures, or characteristics maybe combined in any suitable manner in one or more embodiments.

FIGS. 1A and 1B together illustrate an embodiment of a small scale(e.g., handheld) gas analysis device 100. Device 100 includes asubstrate 102 on which are mounted a fluid handling assembly 101, acontroller 126 coupled to the individual elements within fluid handlingassembly 101, and a reading and analysis circuit 128 coupled to detectorarray 110 and to controller 126. The embodiment shown in the figuresillustrates one possible arrangement of the elements on substrate 102,but in other embodiments the elements can, of course, be arranged on thesubstrate differently.

Substrate 102 can be any kind of substrate that provides the requiredphysical support and communication connections for the elements ofdevice 100. In one embodiment, substrate 102 can be a printed circuitboard (PCB) of the single-layer variety with conductive traces on itssurface, but in other embodiments it can be a PCB of the multi-layervariety with conductive traces in the interior of the circuit board. Inother embodiments, for example an embodiment where device 100 is builtas a monolithic system on a single die, substrate 102 can be chip orwafer made of silicon or some other semiconductor. In still otherembodiments, substrate 102 can also be a chip or wafer in which opticalwaveguides can be formed to support optical communication between thecomponents of device 100.

Fluid handling assembly 101 includes a filter and valve assembly 104, apre-concentrator 106, a gas chromatograph 108, a detector array 110 anda pump 112. Elements 104-112 are fluidly coupled in series: filter andvalve assembly 104 is fluidly coupled to pre-concentrator 106 by fluidconnection 116, pre-concentrator 106 is fluidly coupled to gaschromatograph 108 by fluid connection 118, gas chromatograph 108 isfluidly coupled to detector array 110 by fluid connection 120, anddetector array 110 is coupled to pump 112 by fluid connection 122. Asfurther described below, in one embodiment of device 100 elements104-112 can be micro-electro-mechanical (MEMS) elements or MEMS-basedelements, meaning that some parts of each device can be MEMS and otherparts not. In other embodiments of device 100, some or all of elements104-112 need not be MEMS or MEMS-based, but can instead be some non-MEMSchip scale device.

As indicated by the arrows in the figures, the fluid connections betweenelements 104-112 allow a fluid (e.g., one or more gases) to enter filterand valve assembly 104 through inlet 114, flow though elements 104-112,and finally exit pump 112 through outlet 124. Fluid handling assembly101 also includes a shroud or cover 112 that protects individualelements 104-112. In the illustrated embodiment, channels formed inshroud 112 provide the fluid connections between the elements, but inother embodiments the fluid connections between elements can be providedby other means, such as tubing. In still other embodiments shroud 112can be omitted.

Filter and valve assembly 104 includes an inlet 114 and an outletcoupled to fluid connection 116 such that fluid exiting filter and valveassembly 104 flows into pre-concentrator 110. Filter and valve assembly104 includes a filter to remove particulates from fluid entering throughinlet 114. In embodiments of device 100 where one or more of elements104-112 is a MEMS element, the small scale of parts within the MEMSelements of device pre-concentrator means that fluid entering throughinlet 114 can be filtered to remove these particles so that theparticles do not enter the MEMS devices and either damage them or renderthem inoperative. In embodiments of device 100 that include no MEMScomponents or where fluid entering inlet 114 contains no particles, forinstance because it has been pre-filtered externally to device 100, thefilter portion of filter and valve assembly 104 can be omitted.

Filter and valve assembly 104 also includes a valve so that further flowthrough inlet 114 into fluid handling assembly 101 can be stopped oncesufficient fluid has passed through the device. Stopping further flowthrough inlet 114 prevents dilution of fluids that will flow out ofpre-concentrator 106 during later operation of device 100 (seedescription of operation below). In other embodiments, filter and valveassembly 104 can also include a de-humidifier to remove water vapor fromthe fluid entering through inlet 114, thus improving the accuracy andsensitivity of device 100.

Pre-concentrator 106 includes an inlet coupled to fluid connection 116and an outlet coupled to fluid connection 118. Pre-concentrator 106receives fluid from filter and valve assembly 104 through fluidconnection 116 and outputs fluid to gas chromatograph 108 through fluidconnection 118. As fluid flows through pre-concentrator 106, thepre-concentrator absorbs certain chemicals from the passing fluid, thusconcentrating those chemicals for later separation and detection. In oneembodiment of device 100 pre-concentrator 106 can be a MEMSpre-concentrator, but in other embodiments pre-concentrator 106 can be anon-MEMS chip scale device. Further details of an embodiment of a MEMSpre-concentrator are described below in connection with FIG. 2.

Gas chromatograph 108 includes an inlet coupled to fluid connection 118and an outlet coupled to fluid connection 120. Gas chromatograph 108receives fluid from pre-concentrator 106 through fluid connection 118and outputs fluid to detector array 110 through fluid connection 120. Asfluid received from pre-concentrator 106 flows through gas chromatograph108, individual chemicals in the fluid received from thepre-concentrator are separated from each other in the time domain forlater input into detector array 110. In one embodiment of device 100 gaschromatograph 108 can be a MEMS gas chromatograph, but in otherembodiments gas chromatograph 108 can be a non-MEMS chip scale device.Further details of an embodiment of a MEMS gas chromatograph 108 aredescribed below in connection with FIGS. 3A-3B.

Detector array 110 includes an inlet coupled to fluid connection 120 andan outlet coupled fluid connection 122. Detector array 110 receivesfluid from gas chromatograph 108 through fluid connection 120 andoutputs fluid to pump 112 through fluid connection 122. As fluid flowsthrough detector array 110, the chemicals that were time-domainseparated by gas chromatograph 108 enter the detector array and theirpresence and/or concentration is sensed by sensors within the detectorarray. In one embodiment of device 100 detector array 110 can be a MEMSdetector array, but in other embodiments detector array 110 can be anon-MEMS chip scale device. Further details of an embodiment of adetector array 110 are described below in connection with FIG. 4.

Pump 112 includes an inlet coupled to fluid connection 122, as well asan outlet coupled to an exhaust 124, such that pump 112 draws fluid fromdetector array 110 through fluid connections 122 and returns it to theatmosphere through exhaust 124. Pump 112 can be any kind of pump thatmeets the size and form factor requirements of device 100, provides thedesired flow rate and flow rate control, and has adequate reliability(i.e., an adequate mean time between failures (MTBF)). In oneembodiment, pump 112 can be a MEMS or MEMS-based pump, but in otherembodiments it can be another type of pump. Examples of pumps that canbe used include small axial pumps (e.g., fans), piston pumps, andelectro-osmotic pumps.

Controller 126 is communicatively coupled to the individual elementswithin fluid handling assembly 101 such that it can send control signalsand/or receive feedback signals from the individual elements. In oneembodiment, controller 126 can be an application-specific integratedcircuit (ASIC) designed specifically for the task, for example a CMOScontroller including processing, volatile and/or non-volatile storage,memory and communication circuits, as well as associated logic tocontrol the various circuits and communicate externally to the elementsof fluid handling assembly 101. In other embodiments, however,controller 126 can instead be a general-purpose microprocessor in whichthe control functions are implemented in software. In the illustratedembodiment controller 126 is electrically coupled to the individualelements within fluid handling assembly 101 by conductive traces 130 onthe surface or in the interior of substrate 102, but in otherembodiments controller 126 can be coupled to the elements by othermeans, such as optical.

Readout and analysis circuit 128 is coupled to an output of detectorarray 110 such that it can receive data signals from individual sensorswithin detector array 110 and process and analyze these data signals. Inone embodiment, readout and analysis circuit 128 can be anapplication-specific integrated circuit (ASIC) designed specifically forthe task, such as a CMOS controller including processing, volatileand/or non-volatile storage, memory and communication circuits, as wellas associated logic to control the various circuits and communicateexternally. In other embodiments, however, readout and analysis circuit128 can instead be a general-purpose microprocessor in which the controlfunctions are implemented in software. In some embodiments readout andanalysis circuit 128 can also include signal conditioning and processingelements such as amplifiers, filters, analog-to-digital converters,etc., for both pre-processing of data signals received from detectorarray 110 and post-processing of data generated or extracted from thereceived data by readout and analysis circuit 128.

In the illustrated embodiment, readout and analysis circuit 128 iselectrically coupled to detector array 110 by conductive traces 132positioned on the surface or in the interior of substrate 102, but inother embodiments controller 126 can be coupled to the elements by othermeans, such as optical means. Readout and analysis circuit 128 is alsocoupled to controller 126 and can send signals to, and receive signalsfrom, controller 126 so that the two elements can coordinate andoptimize operation of device 100. Although the illustrated embodimentshows controller 126 and readout and analysis circuit 128 as physicallyseparate units, in other embodiments the controller and the readout andanalysis circuit could be combined in a single unit.

In operation of device 100, the system is first powered up and anynecessary logic (i.e., software instructions) is loaded into controller126 and readout and analysis circuit 128 and initialized. Afterinitialization, the valve in filter and valve unit 104 is opened andpump 112 is set to allow flow through the fluid handling assembly. Fluidis then input to fluid handling assembly 101 through inlet 114 at acertain flow rate and/or for a certain amount of time; the amount oftime needed will usually be determined by the time needed forpre-concentrator 106 to generate adequate concentrations of theparticular chemicals whose presence and/or concentration are beingdetermined. As fluid is input to the system through inlet 114, it isfiltered by filter and valve assembly 104 and flows through elements104-112 within fluid handling assembly 101 by virtue of the fluidconnections between these elements. After flowing through elements104-112, the fluid exits the fluid handling assembly through exhaust124.

After the needed amount of fluid has been input through inlet 114, thevalve in filter and valve assembly 104 is closed to prevent furtherinput of fluid. After the valve is closed, a heater in pre-concentrator106 activates to heat the pre-concentrator. The heat releases thechemicals absorbed and concentrated by the pre-concentrator. As thechemicals are released from pre-concentrator 106, pump 112 is activatedto draw the released chemicals through gas chromatograph 108 anddetector array 110 and output the chemicals through exhaust 124.Activation of pump 112 also prevents backflow through fluid handlingassembly 101.

As the chemicals released from pre-concentrator 106 are drawn by pump112 through gas chromatograph 108, the chromatograph separates differentchemicals from each other in the time domain—that is, differentchemicals are output from the gas chromatograph at different times. Asthe different chemicals exit gas chromatograph 108 separated in time,each chemical enters MEMS detection array 110, where sensors in thedetection array detect the presence and/or concentration of eachchemical. The time-domain separation performed in gas chromatograph 108substantially enhances the accuracy and sensitivity of MEMS detectionarray 110, since it prevents numerous chemicals from entering thedetection array at the same time and thus prevents cross-contaminationand potential interference in the sensors within the array.

As individual sensors within MEMS detection array 110 interact with theentering time-domain-separated chemicals, the detection array senses theinteraction and outputs a signal to readout and analysis circuit 128,which can then use the signal to determine presence and/or concentrationof the chemicals. When readout and analysis circuit 128 has determinedthe presence and/or concentration of all the chemicals of interest itcan use various analysis techniques, such as correlation and patternmatching, to extract some meaning from the particular combination ofchemicals present and their concentrations.

FIG. 2A illustrates an embodiment of a MEMS pre-concentrator 200 thatcan be used as pre-concentrator 106 in device 100. Pre-concentrator 200includes a substrate 202 having a cover plate 204 bonded thereto andsealed around the perimeter of the substrate to create a cavity 206.Substrate 202 has formed therein an inlet 208 on one side, an outlet 210on a different side, and pockets 212 having absorbents therein. In oneembodiment, substrate 202 is a silicon substrate, but in otherembodiments substrate 202 can of course be made of other materials.Heater 216 is formed on the side of substrate 202 opposite the sidewhere cover plate 204 is attached.

In an embodiment where substrate 202 is silicon, inlet 208, outlet 210and pockets 212 can be formed using standard photolithographicpatterning and etching. Although the illustrated embodiment shows sevenpockets 212 a-212 g, the number of pockets needed depends on the numberof different chemicals to be absorbed and concentrated, and on thenature of the absorbents used. In an embodiment where each absorbentabsorbs only one chemical, the number of pockets 212 can correspondexactly to the number of chemicals to be absorbed and concentrated, butin other embodiments where each absorbent absorbs only one chemical agreater number of pockets can be used to increase the absorption area.In still other embodiments where each absorbent can absorb more than onechemical, a lesser number of pockets can be used.

Each pocket 212 has a corresponding absorbent 214 in its interior—pocket212 a has absorbent 214 a, pocket 212 b has absorbent 214 b, and so on.Although shown in the illustrated embodiment as a granular absorbent, inother embodiments absorbents 214 can be coatings on the walls of pockets212 or can be a continuous substance that partially or fully fills eachpocket 212. Other embodiments can include combinations of granular, wallcoatings or continuous filling absorbents. Each absorbent can have achemical affinity for one or more particular chemicals, meaning that theexact absorbents used will depend on the number and nature of chemicalsto be absorbed and concentrated. Examples of absorbents that can be usedinclude cabopack B, cabopack X, etc.

During operation of MEMS pre-concentrator 200 in device 100, fluid fromfilter and valve assembly 104 enters through inlet 208, passes throughabsorbent 214 a in pocket 212 a, and enters cavity 206. Cover plate 204helps guide fluid entering the cavity 206 into the different pockets 212b-212 g and through absorbents 214 b-214 g, until the fluid, minus thechemicals absorbed by absorbents 214 a-214 g, exits the pre-concentratorthrough outlet 210. Once enough fluid has flowed through thepre-concentrator, the valve in filter and valve assembly 104 is closedto prevent further flow through inlet 208. Heater 216 is then activated.Heater 216 heats absorbents 214 a-214 f, causing them to release theabsorbed chemicals through processes such as outgassing. Simultaneouslywith activating heater 216, or shortly thereafter, pump 112 isactivated, drawing the released chemicals out through outlet 210 to gaschromatograph 108.

FIG. 2B illustrates an alternative embodiment of a MEMS pre-concentrator250. MEMS pre-concentrator 250 is in many respects similar to MEMSpre-concentrator 200. The primary difference between the two is that inMEMS pre-concentrator 250, the cover plate 252 is directly bonded to thesubstrate 202 without formation of cavity 206 found in cover plate 204.In one embodiment of MEMS pre-concentrator 250, channels/openings 252can exist in substrate 202 between the different pockets 212 to allowthe fluid to flow through adjacent pockets. In operation of MEMSpre-concentrator 250, fluid enters through inlet 208, passes through thedifferent pockets 212 a-212 g via the channels/openings 252 between thepockets, and finally exits the pre-concentrator through outlet 210.

FIGS. 3A-3B illustrate an embodiment of a MEMS gas chromatograph 300that can be used as gas chromatograph 108 in device 100. MEMS gaschromatograph 300 includes a substrate 302 with an inlet 306 on oneside, an outlet 308 on a different side, and a separation column 310having a stationary phase coating on its walls. A cover plate 304 isbonded to substrate 302 to seal column 310. In one embodiment substrate302 is a silicon substrate, but in other embodiments substrate 302 canof course be made of other materials. In an embodiment where substrate302 is silicon, inlet 306, outlet 308 and column 310 can be formed usingstandard photolithographic patterning and etching, such as deep reactiveion etching (DRIE). Heater 314 is formed on the side of substrate 302opposite the side where cover plate 204 is attached.

Column or channel 310 provides a continuous flow path from inlet 306 tooutlet 308, and some or all of the walls of column 310 are coated with astationary phase coating that can interact with the chemicals beingseparated by the chromatograph or, in other words, the column walls arecoated with specific materials that have specific selectivity/separationpower for the desired gas analysis. How thoroughly and how fastchemicals are separated from the fluid depend on the stationary phasecoating, the overall path length of column 310, and the temperature. Fora given stationary phase coating, the longer the column the better thechemical spectrum separation, but a long column also extends theseparation time. For a given application, the required path length willtherefore usually be determined by a tradeoff among the coating, thecolumn length and the temperature. The illustrated embodiment showscolumn 310 as a spiral column in which the column path length willdepend on the number of coils in the spiral. In other embodiments,however, column 310 can be shaped differently. In one embodiment, column310 can be between 1 m and 10 m in length, but in other embodiment canbe outside this range. In the illustrated MEMS GC, column 310 can beformed by micromachining or micro-electro-mechanical-systems (MEMS)process on silicon wafer, glass wafer, PCB board, or any type ofsubstrate.

During operation of MEMS gas chromatograph 300 in device 100, fluid frompre-concentrator 106 enters through inlet 306 and passes through column310. As fluid passes through the column 310, the different chemicals inthe fluid interact with stationary phase coating 312 at different rates,meaning that the chemicals are separated after traveling through thecolumn, with the chemicals that interact strongly with the stationaryphase being separated first and the chemicals that interact weakly withthe stationary phase being separated last. In other words, chemicalsthat interact strongly with the stationary phase are retained longer inthe stationary phase, while chemicals that interacted weakly with thestationary phase retained less time in the stationary phase. In someembodiments of gas chromatograph 300 this time-domain separation canoccur according to molecular weight (e.g., chemicals with the lowestmolecular weight are separated first, followed by higher molecularweights), but in other embodiments it can occur according to otherchemical characteristics or other separation mechanisms. As thechemicals are time-domain separated, pump 112 draws them out of MEMS gaschromatograph 300 through outlet 308. Generally, the chemicals exitthrough outlet 308 in the reverse order of their separation—that is,chemicals with low retention time exit first, while chemicals withhigher retention times exit later. After leaving outlet 308, thechemicals enter detector array 110.

FIGS. 4A-4B illustrate an embodiment of a detector array 400 that can beused as detector array 110 in device 100. Detector array 400 includes asubstrate 402 with an array of sensors S1-S9 formed thereon. In theillustrated embodiment sensors S1-S9 form a regularly shaped 3-by-3array of sensors, but in other embodiments the sensor array can have agreater or lesser number of sensors, and the sensors can be arranged inany pattern, regular or irregular.

A cover 404 is bonded to the perimeter of substrate 402 to form a cavity410 within which sensors S1-S9 are located. Cover 404 also includes aninlet 406 through which fluid can enter from gas chromatograph 108 andan outlet 408 through which fluid can exit to pump 112. A heater 412 isformed on the side of substrate 402 opposite the side where cover 404 isattached to control the temperature of detector array 400, and hence thesensors within the detector array, during operation. Although not shownin the figure, detector array 400 of course includes outputs by whichsignals generated by sensors S1-S9 can be output for processing.

Each sensor S1-S9 includes a surface with a coating thereon. Eachcoating used will have an affinity for one or more of the particularchemicals being detected, such that the coating absorbs or chemicallyinteracts with its corresponding chemical or chemicals. The interactionbetween coating and chemical in turn changes a physical property of thesensor such as resonant frequency, capacitance or electrical resistance,and that changed physical property of the sensor can be measured using atransducer or other measurement device. The particular coatings chosenfor sensors S1-S9 will depend on the chemicals that sensor array 110will be used to detect. The chemical affinity of coatings also variesstrongly with temperature, so that the operating temperature rangeshould be considered in selecting coatings. In an embodiment wheresensor array 110 will be used to detect volatile organic compounds inhuman breath—such as benzene, toluene, n-octane, ethylbenzene,m,p-xylene, α-pinene, d-limonene, nonanal, and benzaldehyde,2-methylhexane, 4-methyloctane, and so on—coatings that can be used indifferent applications include amorphous copolymers of2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole (PDD) andtetrafluoroethylene (TFE), PtCl2 (olefin), C8-MPN, etc.

Although the illustrated embodiment has nine sensors, the number ofsensors needed depends on the number of different chemicals to bedetected, and on the nature of the coatings used on the sensors. In anembodiment where each coating absorbs or chemically interacts with onlyone chemical the number of sensors can correspond exactly to the numberof chemicals to be detected, but in other embodiments it can bedesirable to have a given coating on more than one sensor forredundancy. In most cases, however, there is no one-to-one correlationbetween chemicals to coatings; in other words, each coating reacts withmore than one different chemical and the reaction between differentchemicals and a given coating will vary in nature and strength. Adetector array having sensors with different coatings is thereforeuseful because the response of the detector array can have differentpatterns for different gases.

In one embodiment of sensor array 400, sensors S1-S9 are MEMS sensorspositioned on the surface of substrate 402, meaning that they aresurface micromachined sensors. In other embodiments using MEMS sensors,however, sensors S1-S9 can be bulk micromachined sensors, meaning thatat least some of the MEMS sensors are formed within substrate 402instead of on the surface. Still other embodiments of sensor array 110using MEMS sensors can include combinations of surface-micromachined andbulk-micromachined sensors. Different types of MEMS sensors can be used,depending on the application and the required sensitivity. Examples ofMEMS sensors that can be used include chemiresistors, bulk acoustic wave(BAW) sensors, etc. In other embodiments of detector array 400, one ormore of sensors S1-S9 can be a non-MEMS sensor. Examples of non-MEMSsensors that can be used in detector array 400 include quartz crystalmicrobalance (QCM) or surface acoustic wave (SAW) sensors with quartz orGallium Arsenide (GaAs) substrates.

During operation of MEMS detector array 400 in device 100, fluid fromgas chromatograph 108 enters through inlet 406 and passes into cavity410. Fluid entering cavity 410 carries time-domain separated chemicals.As each chemical enters cavity 410 it interacts with one or more sensorswhose coating has an affinity for that chemical. The interaction of thechemical with the sensor is sensed and measured, and the presence andconcentration of the particular chemical can be extracted. As more fluidflows into cavity 410, the first chemical is pushed out of cavity 410through outlet 408 and fluid with the next time-domain-separatedchemical enters cavity 410, interacts with the sensor array and ismeasured. This process continues until all the time-domain-separatedchemicals from gas chromatograph 108 have flowed through detector array110. In some embodiments where the affinity of the coatings for theirchemicals is not strong, detector array 110 can be re-usable: after alltime-domain-separated chemicals have been sensed, heater 412 can beactivated to heat the sensors and cause the coatings to release therespective chemicals with which they interacted, making the interactionreversible. In embodiments where the affinity of each coating for itschemicals could be strong, heating of the sensor array could helprelease the partially absorbed gas from the coating materials.

FIG. 5 illustrates an embodiment of a system 500 using an alternativeembodiment of a MEMS-based gas analysis device 502. Device 502 is inmost respects similar to device 100. The primary difference betweendevice 502 and device 100 is the presence in device 502 of a wirelesstransceiver circuit 504 and an antenna 506 mounted on substrate 102.Wireless transceiver circuit 504 can both transmit (Tx) data and receive(Rx) data and is coupled to reading and analysis circuit 128 and antenna506.

In one embodiment of system 500, transceiver 504 can be used towirelessly transmit raw data from reading and analysis circuit 128 toone or both of a router 508 and a computer 510. When transmitted torouter 508, the data can then be re-transmitted to another destinationfor analysis. For example, in an application where device 502 is usedfor health-related chemical analysis, data sent to router 508 can bere-transmitted to one or more of a doctor's office, a hospital, agovernment health department, or someplace else for analysis andinterpretation. After analysis is complete, or if there is a problemwith the data, the doctor's office, hospital or health department cansend instructions to device 502 through router 508, antenna 506 andtransceiver 504 to signal the result, to try to fix or improve the data,or to signal that the test must be performed again.

Continuing with the same health-care example, in the same or anotherembodiment of system 500, wireless transceiver 504 can be used totransmit raw data to computer 510. Computer 510 can either forward theraw data to a doctor, hospital, etc., as did the router, or can analyzethe data with software installed thereon to provide extract informationfrom the data, such as one or more possible medical diagnoses, andprovide the extracted information to the user of device 502. When itprovides analysis and medical diagnoses, computer 510 can also forwardthe diagnosis, alone or with the analysis and raw data, on to thedoctor, hospital, etc. As with the router, the doctor's office, hospitalor health department can send instructions to device 502 throughcomputer 510, antenna 506 and transceiver 504 to try to fix or improvethe data, to signal that the test must be performed again, and so on.

Again continuing with the same health-care example, in still anotherembodiment of system 500 the raw data can be processed, and informationsuch as potential diagnoses extracted from the data, by reading andanalysis circuit 128. The potential diagnoses determined by reading andanalysis circuit 128 can then be sent to computer 510 to be reviewed bythe user and/or forwarded, or can be immediately forwarded alone or withthe supporting raw data to the doctor's office, etc.

FIG. 6 illustrates an embodiment of a system 600 using an alternativeembodiment of a MEMS-based gas analysis device 602. Device 602 is inmost respects similar to device 502. The primary difference betweendevice 502 and device 602 is that the wireless transceiver circuit 504and antenna 506 are replaced with a hardware data interface 604 coupledto reading and analysis circuit 128. In one embodiment, hardware datainterface 604 could be a network interface card, but in otherembodiments hardware data interface can be an Ethernet card, a simplecable plug, etc. External devices can be connected to device 602 throughtraditional means such as cables. Although it has a differentcommunication interface, device 602 and system 600 have all the samefunctionality as device 502 and system 500. As with system 500, insystem 600 MEMS-based gas analysis device 602 can transmit data to, andreceive data from, one or both of a computer 608 and a wireless device606, such as a cell phone or personal digital assistant (PDA). Whentransmitted to wireless device 606 the data can then be forwarded to adoctor's office, hospital, or government health department, and therecipients of the data can in turn send data or instructions back to gasanalysis device 602 through the wireless device. As in system 500, whendata is transmitted to computer 608 it can be forwarded or can beanalyzed by the computer and the result displayed for the user and/orforwarded, and instructions can be transmitted to device 602 throughcomputer 608. Similarly, the data from gas analysis device 602 can beanalyzed by reading and analysis circuit 128. After analysis by circuit128, the extracted information (e.g., one or more diagnoses) and/or theraw data can be forwarded via the hardware data interface 604.

FIG. 7 illustrates an alternative embodiment of a MEMS-based gasanalysis device 700. Device 700 is in most respects similar to device100. The primary difference between system 700 and device 100 is thatdevice 700 includes an on-board display 702 for conveying to a user theresults of the analysis performed by reading and analysis circuit 128.

The illustrated embodiment uses an on-board text display 702, forexample an LCD screen that can convey text information to a user. Forexample, in a health care example display 702 could be used to displaythe test results in analog numbers indicating the situation of patients.Display 702 could indicate a positive or negative diagnosis, couldindicate probabilities of a given diagnosis, or could indicate the rawdata from the detector array. In another health care embodiment, simplerdisplays can be used, such as one with three lights that indicate apositive, negative, or indeterminate result depending on which light isswitched on.

FIG. 8 illustrates an alternative embodiment of a MEMS-based gasanalysis device 800. Device 800 is in most respects similar to device100. The primary difference between device 800 and device 100 is that indevice 800 one or more elements of fluid handling assembly 101 arereplaceable. In the illustrated embodiment, the elements are madereplaceable by mounting them onto substrate 102 using sockets: filterand valve assembly 104 is mounted to substrate 102 by socket 804,pre-concentrator is mounted to substrate 102 by socket 804, gaschromatograph 108 is mounted to substrate 102 by socket 808, detectorarray 110 is mounted to substrate 102 by socket 810, and pump 112 ismounted to substrate 102 by socket 812. In one embodiment, sockets804-812 are sockets such as zero insertion force (ZIF) sockets thatpermit easy replacement by a user, but in other embodiments other typesof sockets can be used. Although the illustrated embodiment shows allthe components of fluid handling assembly 101 being replaceable, inother embodiments only some of the components such as pump 112 anddetector array 110 can be made replaceable.

FIG. 9 illustrates an alternative embodiment of a MEMS-based gasanalysis device 900. Gas analysis device 900 is in most respects similarto device 100. The primary difference between device 900 and device 100is that device 900 includes provisions for an external pre-concentrator902 (i.e., a pre-concentrator not mounted on substrate 102). In theembodiment shown, a valve 904 is placed between pre-concentrator 106 andgas chromatograph 108, and provisions are made to attach externalpre-concentrator 902 to the valve. Valve 904 allows the user to useexternal pre-concentrator 902 instead of, or in addition to, on-boardpre-concentrator 106. In one embodiment external pre-concentrator 902 isa breath collection bag, but in other embodiments it can be somethingdifferent. In an alternative embodiment of device 900 (not shown),pre-concentrator 106 can be permanently removed and replaced by externalpre-concentrator 902. In another embodiment where externalpre-concentrator 902 replaces pre-concentrator 106, instead of insertinga valve between pre-concentrator 106 and gas chromatograph 108, externalpre-concentrator 902 can be coupled upstream of the filter and valveassembly 104.

FIG. 10 illustrates an embodiment of a gas analysis system 1000including a front-end pre-concentrator module 1002 coupled to a gasanalysis subsystem 1004. Embodiments of system 1000 can be used in placeof, or one or more of its components can be used to supplement,filter/valve 104, pre-concentrator 106, gas chromatograph (GC) 108 anddetector 110 in gas analysis systems such as the ones shown in FIGS.1A-1B and 5-9. Similarly, front-end pre concentrator module 1002 can beused in place of, or one or more of its components can be used tosupplement, filter/valve 105 and pre-concentrator 106, while gasanalysis subsystem 1004 can be used in place of, or one or more of itscomponents can be used to supplement, GC 108 and DA 110.

Front-end pre-concentrator module 1002 includes a filter 1006 coupled tofluid connection 1008 by a switch valve SV1. Fluid connection 1008 isalso coupled to the first port of a three-way valve TV1. The second portof three-way valve TV1 is coupled by fluid connection 1010 to the inletof a trap 1011, and the outlet of trap 1011 is coupled to a fluidconnection 1012. The third port of three-way valve TV1 is coupled byfluid connection 1014 to the inlet of a pre-concentrator (PC) 1015, andthe outlet of PC 1015 is coupled by fluid connection 1016 to the firstport of a second three-way valve TV2. The second port of three-way valveTV2 is coupled by fluid connection 1018 to a second switch valve SV2,and SV2 is in turn coupled by fluid connection 1020 to an inlet of pumpP1. An outlet of pump P1 is coupled to fluid connection 1022. The thirdport of three-way valve TV2 is coupled by fluid connection 1024 to gasanalysis subsystem 1004.

In one embodiment of front-end pre-concentrator module 1002, fluidconnection 1008 is a temperature-controlled tube that can be heated to adesired temperature so that the moisture and chemicals/VOCs from breathdo not condense before reaching PC 1015, but in other embodiments itneed not be temperature controlled. In one embodiment, all the fluidconnections between the components are made using volatile organiccompound (VOC)-free materials that do not absorb or emit VOCs or anycontaminants. Teflon is one example of such a material, but in otherembodiments other materials are possible.

In one embodiment of pre-concentrator module 1002, all the componentsare small-scale components, such as micro-scale ormicro-electromechanical system (MEMS) components, but in otherembodiment the individual components, or any combination of theindividual components, need not be small scale. Hence, although theprefix “micro” is used to describe various embodiments or theircomponents, use of the prefix should not be interpreted as any kind ofsize limitation.

Gas analysis subsystem 1004 includes a gas chromatograph (GC) 1026 whoseinlet is coupled to the outlet of front-end pre-concentrator module 1002by fluid connection 1024. The outlet of GC 1026 is coupled by fluidconnection 1028 to the inlet of a detector 1030. The outlet of detector1030 is coupled to a third switch valve SV3 by fluid connection 1032,and switch valve SV3 can be coupled to further components by fluidconnection 1034. For example, in an embodiment where system 1000 is usedin the gas analysis systems shown and described for FIGS. 1A-1B and 5-9,or where gas analysis subsystem 1004 is used in such system, fluidconnection 1034 can couple switch valve SV3 to a pump and switch valveSV3 can be used to control flow through gas analysis subsystem 1004. Inoperation, when front-end pre-concentrator module 1002 is operated inrelease mode (see below), chemicals/VOCs collected in PC 1015 arereleased due to thermal desorption and carried by the clean air throughfluid connection 1024 to gas analysis subsystem 1004. Once in gasanalysis subsystem 1004, the chemicals are separated by GC 1026 anddirected into detector 1030, where they are sensed.

Front-end pre-concentrator module 1002 has different modes of operation,depending on how the three-way valves and switch valves are configured.Four of these modes are: breath collection mode, dry purge mode, releasemode and clean/dry air supply mode. Breath collection mode uses the flowpath shown by dotted line {circle around (1)}. As shown in the figure,three-way valves TV1 and TV2 are switched to direct gas containingchemicals/VOCs from filter 1006 through fluid connections 1008 and 1014and valve TV1 into PC 1015 so that the chemicals/VOCs can beconcentrated. Air or moisture that is not collected by PC 1015 isdirectly exhausted fluid connections 1016-1022, valves TV2 and SV2, andpump P1. To obtain such fast flow rate through the front-end PC, pump P1can be a fast sampling pump to assist the gas flow so that normal breathinto the front-end system is achieved. One or more flow control switchvalves are placed in the system, which consistently monitors and adjuststhe flow rate during the breath collection. In an alternativeembodiment, the pump can be adjusted to maintain the desired flow rateinstead of using flow control valve.

Dry purge mode uses flow path shown by dotted line {circle around (2)}.After the breath collection, three-way valve TV1 can be switched toconnect front-end PC 1015 with trap 1011. Sampling pump P1 can be usedto draw ambient air through trap 1011, which filters all undesiredchemicals/VOCs and moisture from the ambient air and results in deliveryof clean dry air to PC 1015. The dry air is used to purge PC 1015 toremove moisture trapped by the PC and is exhausted back to ambientthrough fluid connections 106-1022, valves TV2 and SV2, and pump P. Insituations where moisture is not critical to system sensing, the drypurge process may not be needed.

Release mode is used to release chemicals collected in PC 1015 to gasanalysis subsystem 1004 and uses flow path shown by dotted line {circlearound (3)}. After the breath collection and optional dry purge, thethree-way valve TV2 is switched to connect PC 1015 with gas analysissubsystem 1004 through fluid connection 1024. PC 1015 is then heated todesired temperature at its optimum ramping rate so that chemicals/VOCsconcentrated by PC 1015 are released due to thermal desorption andcarried through fluid connection 1024 to gas analysis subsystem 1004.

Clean/Dry air supply mode uses the flow path shown by the dotted linelabeled {circle around (4)}. In addition to direct breath collection,front-end pre-concentrator module 1002 can also be used to produce cleandry air for inhalation right before breath collection from a subject. Toprovide a dry air supply, three-way valve TV1 is switched to form flowpath between the trap and filter 1006. As shown by flow path {circlearound (4)}, ambient air is filtered by trap 1011, which removes allundesired chemicals/VOCs from ambient air. Any particles in the air canalso be filtered by filter 1006 as well. The resulting clean filteredair can then be inhaled by a test subject so that the backgroundchemicals/VOCs from the environment do not affect or interfere with thesubject's exhaled breath.

FIG. 11 illustrates an embodiment of a filter assembly 1100 that can beused as filter 1006 in front-end pre-concentrator module 1002. Filterassembly 1100 includes an inlet 1102, an outlet 1104, and a filter 1006positioned between the inlet and the outlet to filter raw air enteringthrough inlet 1102 and exhaust filtered air through outlet 1104. In oneembodiment, inlet 1102 can be a replaceable mouthpiece that can bedisposed of after each breath test to eliminate the risk of diseasetransmission. In other embodiments, inlet 1102 can be a permanentmouthpiece but the entire filter assembly 1100 can be disposable. Filter1006 is a filter that can eliminate the breath particles, bacteria,virus from entering the system. In one embodiment, filter 1006 is aHigh-Efficiency Particulate Arrestor (HEPA) filter, but in otherembodiments it can be another type of filter. In still otherembodiments, filter 1006 can be a combination of more than one type offilter.

FIGS. 12A-12B illustrate embodiments of pre-concentrators that can beused as PC 1015 in front-end pre-concentrator module 1002 or in aback-end pre-concentrator module (see FIGS. 13-14). In one embodiment,PC 1015 is small in size (e.g., <=3 cm) for fast heating and but is alsodesigned to allow a normal breath through flow rate so that a correctbreath collection protocol (e.g., 50 cc/sec from breath) can beachieved. To realize such fast flow rates through the PC 1015, pump P1can be a fast sampling pump that assists the gas flow so that normalbreath flow rates into front-end pre-concentrator module 1002 can beachieved.

FIG. 12A illustrate an embodiment of a PC 1200 designed to collect allthe chemicals/VOCs of interest from a person's breath or other gasstreams. PC 1200 has an inlet 1202, an outlet 1026, and one or morepockets 1204 through which fluid flows and is concentrated. In oneembodiment, PC 1200 can have the construction shown and described forFIG. 2A, but in other embodiments it can have the construction shown anddescribed for FIG. 2B or some other construction altogether.

FIG. 12B illustrates an alternative embodiment of a PC 1250. PC 1250includes an inlet 1252, an outlet 1254 and several parallel micro-PCs1256 a-1256 d that extend from the inlet to the outlet. In oneembodiment, each micro-PC 1256 a-1256 d includes one or more pockets1258 and can have a construction like those shown and described forFIGS. 2A-2B, but in other embodiments can have a different construction.In one embodiment, all parallel micro-PCs 1256 a-1256 d have the sameconstruction, but in other embodiment the need not all have the sameconstruction. Moreover, each micro-PC can be constructed to concentratedifferent chemicals/VOCs than the other micro-PCs in PC 1250. Theillustrated embodiment of PC 1250 has four parallel micro-PCs, but otherembodiments of PC 1250 can have a greater or lesser number of micro-PCs.In operation of PC 1250, during collection a carrier gas containingchemicals enters PC 1250 through inlet 1252, flows simultaneouslythrough pockets in each of the parallel micro-PCs 1256 a-1256 d wherechemicals/VOCs are concentrated for later release. During release, cleanair flows through PC 1250 while micro-PCs 1256 a-1256 d can be heated,one at a time or simultaneously, to release the chemicals concentratedin the pockets of each parallel micro-PC.

FIG. 13A illustrates an alternative embodiment of a gas analysis system1300. Embodiments of system 1300 can be used in place of, or one or moreof its components can be used to supplement, filter/valve 104,pre-concentrator 106, gas chromatograph (GC) 108 and detector 110 in gasanalysis systems such as the ones shown in FIGS. 1A-1B and 5-9.Similarly, front-end pre concentrator module 1302 and/or back-endpre-concentrator 1306 can be used in place of, or one or more of itscomponents can be used to supplement, filter/valve 105 andpre-concentrator 106, while gas analysis subsystem 1304 can be used inplace of, or one or more of its components can be used to supplement, GC108 and DA 110.

System 1300 includes a front-end pre-concentrator module 1302 coupled toa gas analysis subsystem 1304 and also coupled to a back-endpre-concentrator module 1306. System 1300 is useful for low-flowconcentrated gas analysis. Unlike the existing breath analysis protocol,which requires an on-site breath sample collection in canister or trapand then analysis performed in designated laboratories, the system'sfront-end breath collection module can retain the collected sample andthen release the collected chemicals/VOCs directly to its back-end gasanalysis module. Either the miniaturized front-end pre-concentratormodule 1302 or back-end module 1306 can be used separately incombination with other chemical/VOC analysis systems.

Fluid connection 1024 couples front-end pre-concentrator module 1302 toboth fluid connection 1308 and fluid connection 1310. Fluid connections1024 and 1308 provide coupling between pre-concentrator module 1302 andgas analysis subsystem 1304, while fluid connections 1024 and 1310provide coupling between pre-concentrator module 1302 and back-endpre-concentrator 1306. Fluid connections 1024, 1308 and 1310 alsoprovide coupling between gas analysis subsystem 1304 and back-endpre-concentrator 1306.

Front-end pre-concentrator module 1302 has a construction similar tofront-end pre-concentrator module 1002 and has four modes of operationsimilar to those of front-end pre-concentrator module 1002: breathcollection mode, shown by flow path {circle around (1)}; dry purge mode,shown by flow path {circle around (2)}; release mode, shown by flow path{circle around (3)}; and dry air supply mode, shown by fluid {circlearound (4)}. Within pre-concentrator module 1302, release mode flow path{circle around (3)} is the same as it is within pre-concentrator module1002, but in system 1300 flow path {circle around (3)} differs afterleaving pre-concentrator module 1302 because of the presence of back-endpre-concentrator 1306.

Gas analysis subsystem 1304 has a construction similar to gas analysissubsystem 1004, the primary difference being that in gas analysissubsystem 1304 the inlet of GC 1026 is now also coupled via fluidconnections 1308 and 1310 to micro-PC 1312 within back-endpre-concentrator 1312.

Back-end pre-concentrator 1306 includes a micro-PC 1312 coupled to fluidconnections 1310 and 1314. Fluid connection 1314 is also coupled to thefirst port of a fourth three-way valve TV4, while the second port ofthree-way valve TV4 is coupled by fluid connection 1316 to a trap 1318,and trap 1318 is further coupled to the atmosphere by fluid connection1320. The third port of three-way valve TV4 is coupled to the inlet ofpump P2 by fluid connection 1322, and the outlet of pump P2 is coupledby fluid connection 1324 to the third port of third three-way valve TV3.The second port of three-way valve TV3 is vented to atmosphere, whilethe first port of three-way valve TV3 is coupled by fluid connection1326 to fluid connection 1314.

Trap 1318 is a trap designed to filter all chemicals/VOCs and moisturefrom the ambient air to prevent them from contaminating thechemicals/VOCs concentrated in micro-PC 1318, or otherwise affecting thefunction of gas analysis subsystem 1304. In one embodiment, trap 1318can be a sorbent trap; sorbent traps are a common approach to produceclean air without moisture or chemicals/VOCs. In other embodiments,however, other types of traps can be used.

Micro-PC 1312 is a pre-concentrator that in some embodiments can havethe construction shown in FIG. 12A or 12B, although in other embodimentsit can have different constructions. In one embodiment, micro-PC 1312has a very small size (only about 10 micro liters in volume) so that itcan reach a desired temperature in a very short heating time fordesorption and analysis and so that it can achieve the highestchemical/VOC concentrations for detection. In one embodiment, a smallback-end micro-PC 1312 has a maximum flow rate in range of a few tensmilliliter per minute (e.g., 30 ml/min), which does not allow micro-PC1312 to be used for direct breath collection because it would requiretoo much time to sample the large volumes (4000 ml) needed for breathcollection; with a flow rate of 30 ml/min, it could take 30 minutes ormore to use micro-PC 1312 to directly collect breath. In an embodimentof front-end PC 1015 sized to have a few milliliters in volume, breathcan be sampled within about 20 seconds with flow rate of about 50ml/sec. The collected chemicals/VOCs are then released by front-end PC1015 to micro-PC 1312 with a relatively slower flow rate (e.g., 30ml/min). Since front-end PC 1015 has only a few milliliters in volume,it only required less than 10 seconds for back-end PC 1312 to collectall the VOCs from the front-end PC. The total sampling time toconcentrate the breath chemicals/VOCs to back-end PC can be achieved inabout 30 seconds with the disclosed embodiments instead of 30 minutes.

Back-end pre-concentrator 1306 has two modes of operation: a collectionmode and a release mode. The collection mode of pre-concentrator 1306operates together with the release mode of pre-concentrator module 1302,hence its flow path is shown by flow path {circle around (3)}, whichalso corresponds to the flow path of the release mode ofpre-concentrator module 1302. With front-end pre-concentrator module1302 in release mode, gas containing chemicals/VOCs exits PC 1015 can bepulled by pump P2 through fluid connection 1016, three-way valve TV2 andfluid connections 1024 and 1310 into micro-PC 1312, where thechemicals/VOCs are further concentrated. Gas leaving micro-PC 1312 ispulled by pump P2 through three-way valve TV4 and fluid connection 1322,and is exhausted by pump P2 into fluid connection 1324 and three-wayvalve TV3. Valve TV3 then vents the gases to the atmosphere.

The release mode of back-end pre-concentrator 1306 follows completion ofthe collection mode. After completion of the collection mode, micro-PC1312 is heated to a desired temperature at its optimum ramping ratewithin a few seconds to release the collected chemicals and three-wayvalves TV2, TV3, and TV4 are switched to allow the air flow shown byflow path {circle around (5)}. Pump P2 draws clean air through trap 1318and three-way valve TV4 and outputs the clean air through fluidconnection 1324, three-way valve TV3 and fluid connections 1326 and 1314into micro-PC 1312. Chemicals and VOCs released by heating micro-PC 1312are carried by the clean air from micro-PC 1312 to the inlet of GC 1026through fluid connections 1310 and 1308. GC 1026 then separates thechemicals and outputs them to detector 1030 for detection by detector1030.

FIG. 13B illustrates another alternative embodiment of a gas analysissystem 1350. System 1350 includes a front-end pre-concentrator module1352 coupled to a gas analysis subsystem 1354 and also coupled to aback-end pre-concentrator module 1356. Like system 1300, system 1350 isuseful for low-flow concentrated gas analysis, and either theminiaturized front-end pre-concentrator module 1302 or back-end module1306 can be used separately in combination with other chemical/VOCanalysis systems. Embodiments of system 1350 can be used in place of, orone or more of its components can be used to supplement, filter/valve104, pre-concentrator 106, gas chromatograph (GC) 108 and detector 110in gas analysis systems such as the ones shown in FIGS. 1A-1B and 5-9.Similarly, front-end pre concentrator module 1352 and/or back-endpre-concentrator module 1356 can be used in place of, or one or more ofits components can be used to supplement, filter/valve 105 andpre-concentrator 106, while gas analysis subsystem 1354 can be used inplace of, or one or more of its components can be used to supplement, GC108 and DA 110.

Front-end pre-concentrator module 1352 includes a filter 1006 coupledthe first port of a first three-way valve TV1. As with pre-concentratormodule 1302, the filter can be coupled to three-way valve TV1 by atemperature-controlled tube. The second port of three-way valve TV1 iscoupled by fluid connection 1364 to a first Y-splitter Y1, and the thirdport of three-way valve TV1 is coupled by fluid connection 1358 to theinlet of pre-concentrator (PC) 1015. In addition to being coupled tothree-way valve TV1, Y-splitter Y1 is coupled by fluid connection 1366to trap 1011 and by fluid connection 1368 to a first switch valve SV1.The outlet of PC 1015 is coupled by fluid connection 1360 to the firstport of a second three-way valve TV2. The second port of three-way valveTV2 is further coupled by fluid connection 1372 to second Y-splitter Y2,and its third port is coupled by fluid connection 1361 to thirdY-splitter Y3. Third Y-splitter Y3 is further coupled to the inlet of GC1026 by fluid connection 1362 and to micro-PC 1312 by fluid connection1384. Second Y-splitter Y2 is coupled to switch valve SV1 by fluidconnection 1370 is also coupled to a first port of third three-way valveTV3 by fluid connection 1374. The second port of three-way valve TV3 iscoupled by fluid connection 1386 to a fifth three-way valve TV5 withinback-end pre-concentrator 1356, while the third port of three-way valveTV3 is coupled to an inlet of pump P by fluid connection 1376. Theoutlet of pump P is coupled by fluid connection 1378 to the first portof a fourth three-way valve TV4 in back-end pre-concentrator 1356.

Front-end pre-concentrator module 1352 has four modes of operation:breath collection mode, shown by flow path {circle around (1)};front-end release mode, shown by flow path {circle around (2)}; back-endrelease mode, shown by flow path {circle around (3)}; and dry air supplymode, shown by fluid {circle around (4)}. As with other embodimentsdescribed herein, flow paths {circle around (1)}-{circle around (4)} canbe created by appropriate configuration of the switch valves, three-wayvalves, and Y-splitters.

Gas analysis subsystem 1354 has a construction similar to gas analysissubsystem 1304, the primary difference being that in gas analysissubsystem 1354 the inlet of GC 1026 is now coupled to front-endpre-concentrator 1352 via Y-splitter Y3 and fluid connections 1361 and1362, and is coupled to back-end pre-concentrator 1356 via Y-splitter Y3and fluid connections 1362 and 1384.

Back-end pre-concentrator 1356 includes a micro-PC 1312 coupled toY-splitter Y3 by fluid connection 1384 and coupled to the third port offourth three-way valve TV5 by fluid connection 1382. Micro-PC 1312 issimilar to micro-PC 1312 described for FIG. 13A and subject to the samevariations. The first port of three-way valve TV5 is coupled by fluidconnection 1380 to the third port of third three-way valve TV4, whilethe second port of three-way valve TV5 is coupled by fluid connection1386 to three-way valve TV3 within the front-end pre-concentrator. Thesecond port of three-way valve TV4 is vented to atmosphere, while thefirst port of three-way valve TV4 is coupled to the outlet of pump P byfluid connection 1378.

Back-end pre-concentrator 1306 has two modes of operation: a collectionmode that operates together with the front-end release mode of front-endpre-concentrator 1352, and a release mode that operates together withthe back-end release mode of front-end pre-concentrator 1352. Hence, thecollection mode of back-end pre-concentrator 1352 is shown in the figureby flow path {circle around (2)}, which corresponds to the front-endrelease mode of the front-end pre-concentrator, and the release mode ofback-end pre-concentrator 1352 is shown by flow path {circle around(3)}, which corresponds to the back-end release mode of the front-endpre-concentrator. As with other embodiments described herein, flow paths{circle around (2)}-{circle around (3)} can be created by appropriateconfiguration of the switch valves, three-way valves, and Y-splitters.

With front-end pre-concentrator module 1352 in its front-end releasemode, gas containing chemicals/VOCs exits PC 1015 can be pulled by pumpP through the fluid connections and components along flow path {circlearound (2)} and into micro-PC 1312, where the chemicals/VOCs are furtherconcentrated. Gas leaving micro-PC 1312 follows the remainder of flowpath {circle around (2)} until it reaches valve TV4, which vents thegases to the atmosphere. With front-end pre-concentrator 1352 in itsback-end release mode, micro-PC 1312 is heated to a desired temperatureat its optimum ramping rate within a few seconds to release thecollected chemicals. Chemicals and VOCs released by heating micro-PC1312 are carried along flow path {circle around (3)} by clean air movedby pump P through the fluid connections and components to the inlet ofGC 1026 through fluid connections 1384 and 1362. GC 1026 then separatesthe chemicals and outputs them to detector 1030 for detection bydetector 1030.

FIG. 13C illustrates another alternative embodiment of a gas analysissystem 1390. Embodiments of system 1390 can be used in place of, or oneor more of its components can be used to supplement, filter/valve 104,pre-concentrator 106, gas chromatograph (GC) 108 and detector 110 in gasanalysis systems such as the ones shown in FIGS. 1A-1B and 5-9.Similarly, front-end pre concentrator module 1392 and/or back-endpre-concentrator 1356 can be used in place of, or one or more of itscomponents can be used to supplement, filter/valve 105 andpre-concentrator 106, while gas analysis subsystem 1354 can be used inplace of, or one or more of its components can be used to supplement, GC108 and DA 110.

System 1390 is in most respects similar to system 1350 shown in FIG.13B. The primary difference is in the front-end pre-concentrator 1392.Pre-concentrator module 1392 differs from pre-concentrator module 1352in that pre-concentrator 1392 omits Y-splitters Y1 and Y2, switch valveSV1, and fluid connections 1368 and 1370. As a result, fluid connectioncouples three-way valve TV2 to three-way valve TV3 and fluid connection1364 coupled three-way valve TV1 to trap 1011. Like front-endpre-concentrator module 1352, front-end pre-concentrator module 1392 hasfour modes of operation: breath collection mode, shown by flow path{circle around (1)}; front-end release mode, shown by flow path {circlearound (2)}; back-end release mode, shown by flow path {circle around(3)}; and dry air supply mode, shown by fluid {circle around (4)}. Aswith other embodiments described herein, flow paths {circle around(1)}-{circle around (4)} can be created by appropriate configuration ofthe switch valves, three-way valves, and Y-splitters. Withinpre-concentrator 1392, however, flow path {circle around (3)} ismodified so that it flows through valve TV1, PC 1015, and valve TV2 asshown instead of flowing through the removed Y-splitters and the fluidconnections and components between them. Outside of pre-concentrator1392, flow path {circle around (3)} is substantially the same as it isin pre-concentrator 1352.

FIG. 14 illustrates an alternative embodiment of a gas analysis system1400 that can be used in situations where moisture is not desired orallowed in the back-end gas analysis system. When the dry purge cannotcompletely eliminate the moisture in front-end PC, or when completemoisture removal reduces the amount of chemicals/VOCs collected by thefront-end PC, an additional moisture extraction from the front-end PCwithout affecting the amount of collected VOCs can be used. Embodimentsof system 1400 can be used in place of, or one or more of its componentscan be used to supplement, filter/valve 104, pre-concentrator 106, gaschromatograph (GC) 108 and detector 110 in gas analysis systems such asthe ones shown in FIGS. 1A-1B and 5-9. Similarly, front-end preconcentrator module 1402 can be used in place of, or one or more of itscomponents can be used to supplement, filter/valve 105 andpre-concentrator 106, while gas analysis subsystem 1404 can be used inplace of, or one or more of its components can be used to supplement, GC108 and DA 110.

System 1400 includes a front-end pre-concentrator module 1402 coupled toa gas analysis subsystem 1404 and also coupled to a back-endpre-concentrator 1406. Gas analysis subsystem 1404 is similar to gasanalysis subsystems 1004 and 1304 and back-end pre-concentrator 1406 issimilar to back-end pre-concentrator 1306. Front-end pre-concentratormodule 1402 is configured similarly to pre-concentrator modules 1002 and1302, the principal differences in pre-concentrator module 1402 beingthe addition of a gas chromatograph (GC) 1408 and the replacement secondswitch valve SV2 with a fifth three-way valve TV5. Three-way valve TV5is has its first port coupled to the second port of second three-wayvalve TV2 and has its third port coupled to pump P1 by fluid connection1020. GC 1408 has its inlet coupled to fluid connection 1024 and itsoutlet coupled to the second port of three-way valve TV5 by fluidconnections 1410 and 1412. Fluid connection 1410 also couplespre-concentrator module 1402 to gas analysis subsystem 1404 and back-endpre-concentrator 1406. Fluid connections 1410 and 1308 provide couplingbetween additional GC 1408 and GC 1026, while fluid connections 1410 and1310 provide coupling between additional GC 1408 and back-endpre-concentrator 1306. Fluid connections 1410, 1308 and 1310 alsoprovide a coupling between GC 1026 and back-end pre-concentrator 1406.

Pre-concentrator module 1402 has five modes of operation. Three of thesemodes are similar to those of front-end pre-concentrator module 1002 and1302: breath collection mode, shown by flow path {circle around (1)};dry purge mode, shown by flow path {circle around (2)}; and dry airsupply mode, shown by flow path {circle around (4)}. The release mode ofpre-concentrator module 1402, shown by flow path {circle around (3)}, issimilar to the release flow path {circle around (3)} of pre-concentratormodules 1002 and 1302, the primary difference being that inpre-concentrator module 1402 flow path {circle around (3)} travels fromfluid connection 1024 into GC 1408 and exits GC 1408 through fluidconnection 1410. After leaving GC 1408, flow path {circle around (3)}carries the flow into and through back-end pre-concentrator 1406 in amanner similar to that shown for back-end pre-concentrator 1306.

Pre-concentrator 1402 also includes a secondary dry-purge mode, shown byflow path {circle around (5)}, that can be used to reduce moisture in PC1015 if the dry-purge shown by flow path {circle around (2)} does notsucceed in extracting enough moisture. Because the secondary dry purgeused GC 1408, it can be used to remove moisture from PC 1015 withoutlosing any chemicals/VOCs collected in PC 1015. In some situations, thesecondary dry purge may not be needed and a direct moisture separationprocess may be applied directly.

During the secondary dry-purge mode, three-way valves TV1 and TV5 areswitched to produce the flow path through trap 1011, front-end PC 1015,GC 1408, and then exhaustion to ambient. PC 1015 is heated to releasechemicals/VOCs as well remaining moisture within the PC. As the releaseVOCs and moisture entering GC 1408, moisture will pass thought the GCand be exhausted to ambient first as shown in FIG. 9. Three-way valvesTV3, TV4, and TV5 are then switched promptly so that remainingchemicals/VOCs follow flow path {circle around (3)} and are channeledand collected by the back-end micro-PC. As a result, no moisture entersor is collected by micro-PC 1312. Once chemicals/VOCs are collected inmicro-PC 1312, three-way valves TV3 and TV4 can be switched so thatback-end pre-concentrator 1406 enters its own release mode, shown byflow path {circle around (6)}. Flow path {circle around (6)} in system1400 is similar to flow path {circle around (5)} in system 1300, in thatit carries chemicals/VOCs from back-end pre-concentrator 1406 into gasanalysis subsystem 1404.

In one embodiment, the front-end PC 1015 can be pulseheated periodicallyto different temperatures and durations in synchronization withswitching the three-way valves to conditionally release differentchemicals/VOCs or moisture to control flow of the desired chemicals/VOCsto back-end micro-PC 1312 (flow path {circle around (3)}) or undesiredchemicals/VOCs or moisture to ambient exhaust (flow path {circle around(5)}). Chemicals/VOCs collected by the back-end micro-PC 1312 are thenreleased and analyzed by gas analysis subsystem 1404 (flow path {circlearound (6)}).

FIG. 15 illustrates an embodiment of a filter assembly 1500. Filterassembly 1500 can be coupled to a breath/gas/chemical storage containeror external pre-concentrator, such as pre-concentrator/breath collectionbag 902 shown in FIG. 9. Alternatively, combined dry filter assembly andmoisture removal compartment can be coupled directly to a gas analysissystem. For example, in the gas analysis systems shown in FIGS. 1A-1Band 5-9 the combined dry filter assembly and moisture removalcompartment can be part of filter/valve 104 or in the gas analysissystem of FIG. 10, 13 or 14, the combined dry filter assembly andmoisture removal compartment can be part of filter/valve 104 can replaceor supplement filter 1006.

Filter assembly 1500 includes a dry filter assembly 1502 coupled to amoisture removal module 1504. In this embodiment, the moisture removalmodule can be a small stand-alone adaptor compartment that bridgesbetween dry filter assembly 1502 and the breath collection container orgas analysis system to which filter assembly 1500 is coupled. As theexhaled breath is first filtered by the dry filter assembly 1502 forparticulates, microbacteria and/or viruses, the air still contains highhumidity (>90%). When the air continues passing through the moistureremoval compartment, the water vapor is further filtered by the saltcompound contained in the compartment. The final dry exhaled air is thencollected by the container or directly analyzed by the system.

Dry filter assembly 1502 includes an inlet 1506, an outlet 1508 and adry filter 1510 positioned between the inlet and the outlet. In oneembodiment, dry filter 1510 can be a HEPA filter, but in otherembodiments dry filter 1510 can be another type of filter or acombination of different types of filters. In one embodiment, inlet 1506can be a disposable mouthpiece through which a patient can breathe intothe filter assembly, while in other embodiments the entire dry filterassembly 1502 can be disposable. In still other embodiments, the entirefilter 1500, including dry filter assembly 1502 and the moisture removalcompartment 1504, can be disposable.

Moisture removal module 1504 includes an inlet 1512, a moisture removalcompartment 1514, and an outlet 1516. In one embodiment, moistureremoval compartment 1514 is packed with compounds with a high affinityfor molecular water, such as small amounts of a salt compound that canabsorb significant amount of water and can be used to effectively absorbmoisture directly from exhaled breath. Examples of salt compounds thatcan be used include lithium chloride (LiCl), lithium bromide (LiBr),lithium iodide (LiI) and sodium bromide (NaBr). In other embodimentsother compounds, such as non-ionic salt compounds, can be used. In oneembodiment the compound can be in powder form, but in other embodimentsit can be in granular form, in porous solid form, or in some other form.In still other embodiments, the compound be coated on a poroussubstrate, and the coated porous substrate is then packed into themoisture removal compartment. In one embodiment, the porous substratecan be a gas-permeable media/membrane such as glass wool, but in otherembodiments other types of porous substrates can be used. The amount ofcompound to be used depends on the amount of sampling air and the numberof iterations before it needs to be replaced or refreshed; in someembodiments only a few grams are needed for 1 L of air sampling. Whenthe humid air flows through the compartment, the salt compound willstrongly attract the water vapor due to its strong water affinity. As aresult, the air that passes through the disclosed moisture removalcompartment will result in a moisture free or low moisture sample at itsoutput.

FIG. 16 illustrate a pair of alternative embodiments 1600 and 1650 of afilter assembly. Filter assemblies 1600 and 1650 include substantiallythe same components as filter assembly 1500, but in filter assembly 1600moisture removal compartment 1514 is integrated into outlet 1508 of dryfilter assembly 1502. In filter assembly 1650, moisture removalcompartment 1514 is instead integrated into inlet 1506 if dry filterassembly 1502.

FIGS. 17A-17B illustrate further embodiments of filters 1700 and 1750that integrate the dry filter with the moisture removal compartment inthe same assembly. In filter assembly 1700, moisture removal compartment1514 is integrated into the main body of dry filter 1502, so that it isin downstream of dry filter 1510. In other embodiments, moisture removalcompartment 1514 can be positioned upstream of dry filter 1510. Infilter 1750, dry filtering and moisture removal are combined in a singlefilter 1752 that can be positioned in a filter assembly between inlet1506 and outlet 1508. Filter 1752 can be formed by coatingwater-absorbing compounds, which can be at least any of the compoundsmentioned above for moisture removal compartment 1514, directly on aporous substrate. In one embodiment the porous substrate can be glasswool, but in others it can be some other type of porous filter orgas-permeable membrane that provides a large surface area of the coatedcompound to the air flow. It can effectively prevent passage of moisturethrough the treated filter, thus achieving dry filtration and moistureremoval in a single filter.

FIG. 18 illustrates an embodiment of a re-usable moisture removalassembly 1800 that can be either couple to or integrated within a gasanalysis system or used as an external apparatus. For example, inembodiments of the gas analysis systems shown in FIGS. 1A-1B and 5-9 themoisture removal assembly can be part of filter/valve 104 or could bepositioned upstream or downstream of filter/valve 104. In the gasanalysis system of FIG. 10, 13 or 14, moisture removal assembly 1800 canreplace or supplement filter 1006. The reusability of such miniaturizedmoisture removal assembly is especially beneficial for a portable gasanalysis system for environment monitoring, where many iterations ofhumid gas sampling may be needed without usage of disposable parts.

Assembly 1800 includes a three-way valve TV1 having a humid air inlet1802 coupled to its first port, a dry air inlet 1804 coupled to itssecond port, and a fluid connection 1806 coupled between its third portand an inlet of moisture removal compartment 1809. Moisture removalcompartment 1809 is similar to compartment 1514 and subject to the samevariations. A fluid connection 1810 is coupled to the outlet of themoisture removal compartment 1809. The absorption and desorption ofwater by salt compound is usually reversible. Molecular water can bedriven away from salt compound by heat treatment, similar to sodiumchloride formation from salt water. Hence, a heater 1808 is coupled tomoisture removal compartment 1809. In one embodiment, heater 1808 can bea separate heater unit, but in other embodiments heater 1808 can beintegrally formed with moisture removal compartment 1809. In still otherembodiments, heat can be applied to moisture removal compartment 1809 insome other way.

In operation, moisture removal assembly 1800 has two modes: removal modeand disposal mode. During removal mode, three-way valve TV1 is set toallow fluid to flow through humid air inlet 1802, fluid connection 1806,moisture removal compartment 1809 and outlet fluid connection 1810, asshown by flow path {circle around (1)} in the figure. During disposalmode, three-way valve TV1 is set to allow fluid to flow through dry airinlet 1804, fluid connection 1806, moisture removal compartment 1809 andoutlet 1810, as shown by flow path {circle around (2)} in the figure. Asdry air flows through the system, heater 1808 is activated to heatmoisture removal compartment 1809 so that water captured in thecompartment is released and carried away through outlet 1810.

FIG. 19 illustrates an alternative embodiment of a reusable moistureremoval assembly 1900 that can be either integrated within a gasanalysis system or used as an external apparatus. Assembly 1900 includesa first three-way valve TV1 having a humid air inlet 1902 coupled to itsfirst port, a dry air inlet 1904 with a trap 1906 coupled to its secondport, and a fluid connection 1908 coupled between its third port and aninlet of moisture removal compartment 1909. Trap 1902 can be a sorbenttrap used to filter all chemicals/VOCs and moisture from the ambient airif the dry air entering through inlet 1804 is directly from theenvironment. A sorbent trap is a common approach to produce clean air,but it cannot selectively remove moisture without also blocking VOCslike the disclosed embodiments using salt compound. Moisture removalcompartment 1909 is similar to compartment 1514 and subject to the samevariations.

A heater 1910 is coupled to moisture removal compartment 1909. In oneembodiment, heater 1910 can be a separate heater unit, but in otherembodiments heater 1910 can be integrally formed with moisture removalcompartment 1909. In still other embodiments, heat can be applied tomoisture removal compartment 1909 in some other way. A fluid connection1912 is coupled from the outlet of the moisture removal compartment 1909to the first port of a second three-way valve TV2. The second port ofthree-way valve TV2 is coupled to an inlet of pump P by fluid connection1914, and the outlet of pump P is coupled to a fluid connection 1916.The third port of three-way valve TV2 is coupled to a fluid connection1918, which can then be coupled to whatever device assembly 1900 is usedwith.

In operation, moisture removal assembly 1900 has two modes of operation:removal mode and disposal mode. During sampling mode, three-way valvesTV1 and TV2 are set to allow fluid to flow through humid air inlet 1902,fluid connection 1908, moisture removal compartment 1909, fluidconnection 1912, three-way valve TV2 and fluid connection 1918, as shownby flow path {circle around (1)} in the figure. During disposal mode,three-way valves TV1 and TV2 are set to allow fluid to flow through dryair inlet 1904, trap 1906, fluid connection 1908, moisture removalcompartment 1909, outlet 1912, three-way valve TV2 and outlet 1914, asshown by flow path {circle around (2)} in the figure. Pump P can be usedto produce a fluid flow for flushing out the system. As dry air flowsthrough the system, heater 1910 is activated to heat moisture removalcompartment 1909 so that water captured in the compartment is releasedand carried away through outlet 1916. After the moisture removalcompartment is refreshed, the apparatus can then be used again insampling mode until the compartment is saturated with water, at whichpoint the assembly is put through another disposal cycle.

Device Applications

Pre-clinical studies on human breath analysis have found that certainvolatile organic compounds (VOCs) of exhaled human breath are correlatedto certain diseases, such as pneumonia, pulmonary tuberculosis (TB),asthma, lung cancer, liver diseases, kidney diseases, etc. Thecorrelations are especially evidential for lung-related diseases.Current analytical systems still rely on large and expensive laboratoryinstruments, such as gas chromatography (GC) and mass spectrometry (MS).Mass spectrometers in particular are impossible to miniaturize, makingwidespread use of these diagnostic instruments impossible.

The embodiments of MEMS-based gas analysis sensors discussed aboveprovide a solution to this problem, and in particular could be usedadvantageously to diagnose and monitor various diseases such as asthma,lung cancer, lung-related diseases, and other non-lung diseases such askidney and liver diseases, and etc.

Asthma

Asthma is a chronic disease; therefore, regularly monitoring patient'sstatus is helpful to doctor on tracking patient's healing progresses.Therefore, the new idea of handheld diagnostics would make the breathanalysis possible done at home or anywhere. In current diagnostics thebasic measurement is peak flow rate and the following diagnosticcriteria are used by the British Thoracic Society, but the peak flowrate is a physical quantity measurement. Breath analysis could providespecific root causes of the bronchi contraction by measuring the VOCsfrom patient's breath. Embodiments of the MEMS-based gas analysissystems could be used to monitor the efficacy of the medication.Furthermore, the medication therapy can be tailored to individualpatient through this active monitoring by using this home-based device.

Tuberculosis

One third of the world's current population has been infected by TB. And75% of the cases are pulmonary TB. The infected rate in the developingcountries is much higher than developed countries. Therefore, there areurgent needs of developing affordable diagnostic devices for developingcountries. Embodiments of the MEMS-based gas analysis system wouldprovide a cost-effective solution. Tuberculosis is caused byMycobacterium. Current diagnostic is time consuming and difficult sinceculturing the slow growing Mycobacterium takes about 6 weeks. Therefore,a complete medical evaluation, including chest X-ray, Tuberculosisradiology, tuberculin skin test, microbiological smears and cultures, isused to get more accurate assessment. Therefore, the rapid diagnostic isvery valuable and our breath analysis approach could achieve such needs.

Lung Cancer

With early detection and treatment, the 5-year survival rate for lungcancer improves dramatically. Current diagnostic methods, such as chestX-ray and CT (computed tomography) scan, are difficult to detect earlystage lung cancer. Breath analysis using embodiments of the MEMS-basedgas analysis system could diagnose the early stage lung cancer.

Classification of Lung-Related Diseases with Similar Symptoms

Breath analysis on exhaled VOCs is viable method to identify patient'slung-related diseases, which has similar symptoms. For example,embodiments of the MEMS-based gas analysis system can provide the testeddata to medical doctors to classify which disease between cool,lung-cancer, or pneumonia the patient would have. Breath analysis wouldbe the first screening test because of its simplicity before going formore tedious diagnostic measurements.

The above description of illustrated embodiments of the invention,including what is described in the abstract, is not intended to beexhaustive or to limit the invention to the precise forms disclosed.While specific embodiments of, and examples for, the invention aredescribed herein for illustrative purposes, various equivalentmodifications are possible within the scope of the invention, as thoseskilled in the relevant art will recognize. These modifications can bemade to the invention in light of the above detailed description.

The terms used in the following claims should not be construed to limitthe invention to the specific embodiments disclosed in the specificationand the claims. Rather, the scope of the invention is to be determinedentirely by the following claims, which are to be construed inaccordance with established doctrines of claim interpretation.

The invention claimed is:
 1. An apparatus comprising: a front-endpre-concentrator module including an inlet, an outlet, and at least onevalve to control flow through the inlet, the outlet, or both, thefront-end pre-concentrator module comprising: a pre-concentrator havingan inlet and an outlet, a first three-way valve coupled to the inlet ofthe pre-concentrator and a second three-way valve coupled to the outletof the pre-concentrator, a trap coupled to the first three way valve, aswitch valve coupled to the second three-way valve, and a pump coupledto the switch valve; a back-end pre-concentrator module including aninlet, an outlet, and at least one valve to control flow through theinlet, the outlet, or both; and a gas analysis module having an inletand an outlet and including a gas chromatograph having an inlet and anoutlet, wherein the outlet of the front-end pre-concentrator and theoutlet of the back-end pre-concentrator are coupled to the inlet of thegas analysis module.
 2. The apparatus of claim 1 wherein the front-endpre-concentrator module further comprises a filter coupled to the firstthree-way valve.
 3. The apparatus of claim 2 wherein the front-endpre-concentrator module further comprises a switch valve coupled betweenthe filter and the first three-way valve.
 4. The apparatus of claim 1wherein the back-end pre-concentrator module comprises: apre-concentrator having an inlet and an outlet, the inlet being coupledto the second three-way valve and to the inlet of the gas chromatograph;a fourth three-way valve coupled to the outlet of the pre-concentrator;a trap coupled to the fourth three-way valve; a second pump coupled tothe fourth three-way valve; and a third three-way valve coupled to thesecond pump and coupled to a fluid connection between the outlet of thepre-concentrator and the fourth three-way valve.
 5. The apparatus ofclaim 4 wherein the back-end pre-concentrator module further comprises avent coupled to the third three-way valve.
 6. The apparatus of claim 1wherein the gas analysis module further comprises a detector coupled tothe outlet of the gas chromatograph.
 7. The apparatus of claim 1 whereinthe gas analysis module further comprises: a detector coupled to theoutlet of the gas chromatograph; a control circuit coupled to the gaschromatograph and to the detector, wherein the control circuit cancommunicate with the gas chromatograph and to the detector; a readoutcircuit coupled to the detector and to the control circuit, wherein thereadout circuit can communicate with the control circuit and thedetector; and a communication interface coupled to the readout circuit.8. The apparatus of claim 7 wherein the readout circuit includes ananalysis circuit and associated logic to analyze the output signalsreceived from the detector.
 9. An apparatus comprising: a front-endpre-concentrator module including an inlet, an outlet, and at least onevalve to control flow through the inlet, the outlet, or both, thefront-end pre-concentrator module comprising: a pre-concentrator havingan inlet and an outlet, a first three-way valve coupled to the inlet ofthe pre-concentrator and a second three-way valve coupled to the outletof the pre-concentrator, a trap coupled to the first three way valve, athird three-way valve coupled to the second three-way valve, and a pumpcoupled to the third three-way valve; a back-end pre-concentrator moduleincluding an inlet, an outlet, and at least one valve to control flowthrough the inlet, the outlet, or both; and a gas analysis module havingan inlet and an outlet and including a gas chromatograph having an inletand an outlet, wherein the outlet of the front-end pre-concentrator andthe outlet of the back-end pre-concentrator are coupled to the inlet ofthe gas analysis module.
 10. The apparatus of claim 9 wherein thefront-end pre-concentrator module further comprises: a first Y-splittercoupled between the first three way valve and the trap; a secondY-splitter coupled between the second three-way valve and the thirdthree-way valve; and a fluid connection between the first Y-splitter andthe second Y-splitter.
 11. The apparatus of claim 10, further comprisinga switch valve coupled between the first Y-splitter and the secondY-splitter.
 12. The apparatus of claim 9 wherein the front-endpre-concentrator module further comprises a filter coupled to the firstthree-way valve.
 13. The apparatus of claim 12 wherein the filter iscoupled to the first three-way valve by a temperature-controlled tube.14. The apparatus of claim 9 wherein the inlet of the gas chromatographis coupled to the second three-way valve by a third Y-splitter.
 15. Theapparatus of claim 14 wherein the back-end pre-concentrator modulecomprises: a pre-concentrator coupled to the third Y-splitter; a fourththree-way valve coupled to the pump and to a vent; and a fifth three-wayvalve coupled to the pre-concentrator, the third three-way valve and thefourth three-way valve.
 16. An apparatus comprising: a front-endpre-concentrator module including an inlet, an outlet, and at least onevalve to control flow through the inlet, the outlet, or both, thefront-end pre-concentrator module comprising: a pre-concentrator havingan inlet and an outlet, a first three-way valve coupled to the inlet ofthe pre-concentrator and a second three-way valve coupled to the outletof the pre-concentrator, a trap coupled to the first three way valve, afifth three-way valve coupled to the second three-way valve and to afirst pump, and an additional gas chromatograph having: an inlet coupledto the second three-way valve, and an outlet coupled to the inlet of thegas chromatograph, to the inlet of the back-end pre-concentrator, and tothe fifth three-way valve; a back-end pre-concentrator module includingan inlet, an outlet, and at least one valve to control flow through theinlet, the outlet, or both; and a gas analysis module having an inletand an outlet and including a gas chromatograph having an inlet and anoutlet, wherein the outlet of the front-end pre-concentrator and theoutlet of the back-end pre-concentrator are coupled to the inlet of thegas analysis module.
 17. The apparatus of claim 16 wherein the front-endpre-concentrator module further comprises a filter coupled to the firstthree-way valve.
 18. The apparatus of claim 17 wherein the filter andthe first three-way valve are coupled by a temperature-controlled tube.19. The apparatus of claim 16 wherein the front-end pre-concentratormodule further comprises a switch valve coupled between the filter andthe first three-way valve.
 20. The apparatus of claim 16 wherein theback-end pre-concentrator module comprises: a pre-concentrator having aninlet and an outlet, the inlet being coupled to the inlet of the gaschromatograph and the outlet of the additional gas chromatograph; afourth three-way valve coupled to the outlet of the pre-concentrator; atrap coupled to the fourth three-way valve; a second pump coupled to thefourth three-way valve; a third three-way valve coupled to the secondpump and coupled to a fluid connection between the pre-concentrator andthe fourth three-way valve.
 21. The apparatus of claim 20 wherein theback-end pre-concentrator module further comprises a vent coupled to thethird three-way valve.
 22. A process comprising: providing an apparatusincluding: a front-end pre-concentrator module including an inlet, anoutlet, and at least one valve to control flow through the inlet, theoutlet, or both, the front-end pre-concentrator module including: apre-concentrator having an inlet and an outlet, a first three-way valvecoupled to the inlet of the pre-concentrator and a second three-wayvalve coupled to the outlet of the pre-concentrator, a trap coupled tothe first three way valve, a second switch valve coupled to the secondthree-way valve, and a pump coupled to the second switch valve; aback-end pre-concentrator module including an inlet, an outlet, and atleast one valve to control flow through the inlet, the outlet, or both;and a gas analysis module having an inlet and an outlet and including agas chromatograph having an inlet and an outlet, wherein the outlet ofthe front-end pre-concentrator and the outlet of the back-endpre-concentrator are coupled to the inlet of the gas analysis module;configuring the at least one valve in the front-end pre-concentrator andthe at least one valve in the back-end pre-concentrator to form a flowpath to receive a gas sample through the front-end pre-concentrator,concentrate chemicals or volatile organic compounds carried by the gasand direct them to the gas analysis module, the back-endpre-concentrator module, or both; and configuring the first and secondthree-way valves to form a flow path to receive a gas sample through thefirst three-way valve and concentrate chemicals or volatile organiccompounds carried by the gas in the pre-concentrator.
 23. The process ofclaim 22, further comprising: heating the pre-concentrator to releasechemicals or volatile organic compounds (VOCs) trapped therein; andconfiguring the second three-way valve to form a flow path through withthe chemicals or VOCs can flow from the pre-concentrator to one or bothof the back-end pre-concentrator module and the gas analysis module. 24.The process of claim 23, further comprising directing chemicals or VOCsconcentrated by the back-end pre-concentrator module into the gasanalysis module.
 25. The process of claim 22, further comprisingproviding a back-end pre-concentrator module comprising: apre-concentrator having an inlet and an outlet, the inlet being coupledto the second three-way valve and to the inlet of the gas chromatograph;a fourth three-way valve coupled to the outlet of the pre-concentrator;a trap coupled to the fourth three-way valve; a second pump coupled tothe fourth three-way valve; a third three-way valve coupled to thesecond pump and coupled to a fluid connection between the outlet of thepre-concentrator and the fourth three-way valve.
 26. A processcomprising: providing an apparatus including: a front-endpre-concentrator module including an inlet, an outlet, and at least onevalve to control flow through the inlet, the outlet, or both, thefront-end pre-concentrator module including: a pre-concentrator havingan inlet and an outlet, a first three-way valve coupled to the inlet ofthe pre-concentrator and a second three-way valve coupled to the outletof the pre-concentrator, a trap coupled to the first three way valve, athird three-way valve coupled to the second three-way valve, and a pumpcoupled to the third three-way valve; a back-end pre-concentrator moduleincluding an inlet, an outlet, and at least one valve to control flowthrough the inlet, the outlet, or both; and a gas analysis module havingan inlet and an outlet and including a gas chromatograph having an inletand an outlet, wherein the outlet of the front-end pre-concentrator andthe outlet of the back-end pre-concentrator are coupled to the inlet ofthe gas analysis module; configuring the at least one valve in thefront-end pre-concentrator and the at least one valve in the back-endpre-concentrator to form a flow path to receive a gas sample through thefront-end pre-concentrator, concentrate chemicals or volatile organiccompounds carried by the gas and direct them to the gas analysis module,the back-end pre-concentrator module, or both; and configuring the firstand second three-way valves to form a flow path to receive a gas samplethrough the first three-way valve and concentrate chemicals or volatileorganic compounds carried by the gas in the pre-concentrator.
 27. Theprocess of claim 26, further comprising: heating the pre-concentrator torelease chemicals or volatile organic compounds (VOCs) trapped therein;and configuring the second three-way valve to form a flow path throughwith the chemicals or VOCs can flow from the pre-concentrator to one orboth of the back-end pre-concentrator module and the gas analysismodule.
 28. The process of claim 27, further comprising directingchemicals or VOCs concentrated by the back-end pre-concentrator moduleinto the gas analysis module.
 29. The process of claim 26, furthercomprising providing a back-end pre-concentrator module comprising: apre-concentrator coupled to the third Y-splitter; a fourth three-wayvalve coupled to the pump and to a vent; and a fifth three-way valvecoupled to the pre-concentrator, the third three-way valve and thefourth three-way valve.
 30. A process comprising: providing an apparatusincluding: a front-end pre-concentrator module including an inlet, anoutlet, and at least one valve to control flow through the inlet, theoutlet, or both, the front-end pre-concentrator module including: apre-concentrator having an inlet and an outlet; a first three-way valvecoupled to the inlet of the pre-concentrator and a second three-wayvalve coupled to the outlet of the pre-concentrator; a trap coupled tothe first three way valve; a third three-way valve coupled to the secondthree-way valve and to a first pump; and an additional gas chromatographhaving: an inlet coupled to the second three-way valve, and an outletcoupled to the inlet of the gas chromatograph, to the inlet of theback-end pre-concentrator, and to the third three-way valve; a back-endpre-concentrator module including an inlet, an outlet, and at least onevalve to control flow through the inlet, the outlet, or both; and a gasanalysis module having an inlet and an outlet and including a gaschromatograph having an inlet and an outlet, wherein the outlet of thefront-end pre-concentrator and the outlet of the back-endpre-concentrator are coupled to the inlet of the gas analysis module;configuring the at least one valve in the front-end pre-concentrator andthe at least one valve in the back-end pre-concentrator to form a flowpath to receive a gas sample through the front-end pre-concentrator,concentrate chemicals or volatile organic compounds carried by the gasand direct them to the gas analysis module, the back-endpre-concentrator module, or both.
 31. The process of claim 30, furthercomprising: heating the pre-concentrator to release chemicals orvolatile organic compounds (VOCs) trapped therein; and configuring thesecond three-way valve to form a flow path through with the chemicals orVOCs can flow from the pre-concentrator to one or both of the back-endpre-concentrator module and the gas analysis module.
 32. The process ofclaim 31, further comprising directing chemicals or VOCs concentrated bythe back-end pre-concentrator module into the gas analysis module. 33.The process of claim 30, further comprising providing a back-endpre-concentrator module comprising: a pre-concentrator having an inletand an outlet, the inlet being coupled to the inlet of the gaschromatograph and the outlet of the additional gas chromatograph; afourth three-way valve coupled to the outlet of the pre-concentrator; atrap coupled to the fourth three-way valve; a second pump coupled to thefourth three-way valve; a fifth three-way valve coupled to the secondpump and coupled to a fluid connection between the pre-concentrator andthe fourth three-way valve.